膠質細胞調節線蟲內質網抗逆性與壽命

膠質細胞調節線蟲內質網抗逆性與壽命

作者：

小柯機器人

發布時間：2020/1/29 16:36:47

美國加州大學伯克利分校Andrew Dillin小組取得一項新進展。他們的研究發現，在秀麗隱杆線蟲中，四個膠質細胞通過神經肽信號來調節內質網的抗逆性和壽命。這一研究成果於2020年1月24日發表在國際頂尖學術期刊《科學》上。

研究人員在星形膠質樣膠質細胞亞群中表達了組成型活躍的內質網未摺疊蛋白反應（UPRER）轉錄因子XBP-1s，從而延長了秀麗隱杆線蟲的壽命。膠質細胞的XBP-1s啟動了遠端細胞中UPRER的強大細胞非自主型激活，並使動物對蛋白質聚集和慢性ER應激更具抵抗力。缺乏神經肽加工和分泌的突變體抑制了UPRER的膠質細胞非自主誘導和壽命延長。因此，星形膠質樣神經膠質細胞在調節機體內質網應激抵抗和長壽中發揮了作用。

據了解，神經系統感知細胞應激並協調蛋白質穩態的能力對於機體的健康至關重要。不幸的是，隨著年齡的增長，緩解蛋白穩態紊亂的應激反應（例如UPRER）會變得無效。

附：英文原文

Title: Four glial cells regulate ER stress resistance and longevity via neuropeptide signaling in C. elegans

Author: Ashley E. Frakes, Melissa G. Metcalf, Sarah U. Tronnes, Raz Bar-Ziv, Jenni Durieux, Holly K. Gildea, Nazineen Kandahari, Samira Monshietehadi, Andrew Dillin

Issue&Volume: 2020/01/24

Abstract: The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans. Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRER and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.

DOI: 10.1126/science.aaz6896

Source: https://science.sciencemag.org/content/367/6476/436

Science：《科學》，創刊於1880年。隸屬於美國科學促進會，最新IF：41.037